Inflammatory bowel disease (IBD) encompasses a group of diseases such as ulcerative colitis (UC) and Crohn's disease (CD). IBDs can be difficult to diagnose. An initial diagnosis, made on the basis of medical history and physical examination, is generally confirmed via imaging tests to look at the intestines and laboratory culture tests to rule out bacterial, viral and parasitic infections. The conditions may go undiagnosed for years because symptoms usually develop gradually and less than all of the intestines may be involved.
Colonoscopy can be used to image the intestines and colon. A doctor uses a thin, lighted endoscope to look at the entire intestines and distinguish between IBDs on the basis of the location of ulcerations. Crohn's disease affects some areas of the intestines and skips over others. Ulcerative colitis is more indiscriminate. Endoscopy is also used to take a biopsy of intestinal tissue, which can be used to identify the deep inflammation of the bowel that is characteristic of Crohn's disease. X-rays (after oral or rectal ingestion of Barium), computed tomography (CT) scan, and magnetic resonance imaging (MRI) may be helpful in locating fistulas.
A stool analysis (including a test for blood in the stool) is often performed, depending on symptoms, to look for blood and signs of bacterial infection. Blood and urine tests may be done to check for anemia, high white cell counts, or malnutrition—all signs of IBDs.
Currently there is no reliable biochemical test available for IBD. Up-regulation of certain cytokines has been detected in tissue and mucosal samples surgically removed from diseased bowel in IBD patients (Indaram A. V. et al., Mucosal cytokine production in radiation-induced proctosigmoiditis compared with inflammatory bowel disease, Am J. Gastroenterol. 2000 95(5):1221-5; McCormack G, et al., Tissue cytokine and chemokine expression in inflammatory bowel disease, Inflamm Res. 2001 50(10):491-5). Up-regulation of a membrane-bound cytokine receptor was also observed in diseased bowel tissue from Crohn's patients (Holtmann M. H. et al., Tumor necrosis factor-receptor 2 is up-regulated on lamina propria T cells in Crohn's disease and promotes experimental colitis in vivo, Eur J Immunol. 2002 32(11):3142-51). The collection of the tissue and mucosal samples requires the use of invasive and potentially dangerous surgical techniques, thus limiting the practical applicability of these measurements for diagnostics. The diagnostic utility of these measurements is also unknown. In addition, at least one report found that cytokine levels do not discriminate between Crohn's disease and ulcerative colitis (Banks C, et al., Chemokine expression in IBD. Mucosal chemokine expression is unselectively increased in both ulcerative colitis and Crohn's disease, J. Pathol. 2003 199(1):28-35).
Increased levels of IL-1β, IL-6 and soluble TNF receptor II were observed in stool samples from mice with chemically induced colitis (Lindsay J. O., et al., IL-10 gene therapy is therapeutic for dextran sodium sulfate-induced murine colitis, Dig Dis Sci. 2004 49(7-8):1327-34). It is not clear whether similar effects occur in human CD and UC patients.
Up-regulation of cytokine levels in the bowel often does not lead to corresponding changes in blood (Abstract of Kmiec Z., Cytokines in inflammatory bowel disease. Arch. Immunol. Ther. Exp. (Warsz). 1998 46(3):143-55). In one study that did report a change in the serum level of a cytokine in IBD, the average serum eotaxin levels for a population of CD and UC patients was shown to be significantly different than the average value calculated for a normal population (Mir A, et al., Elevated serum eotaxin levels in patients with inflammatory bowel disease, Am J. Gastroenterol. 2002 June; 97(6):1452-7). No statistical difference was observed between the CD and UC populations. The results showed a significant overlap in the distribution of levels in the normal and diseased population; the serum level of eotaxin would therefore be expected to be a relatively poor predictor of IBD.